A Solution to a Bioethical Dilemma?

Newly published research may help solve one of the great ethical dilemmas of the modern age of medicine.

With their ability to differentiate into many different human cell types, pluripotent embryonic stem cells have the potential to be used clinically as a regenerative treatment for a variety of diseases and injuries. Despite these apparent benefits, ethical concerns about the destruction of embryos during stem cell harvesting have led to the imposition of restrictions on embryonic stem cell research and have driven scientific investigators to search for alternative sources of pluripotent stem cells. In a study published in the January 30 issue of Nature, researchers at Brigham and Women’s Hospital and Japan’s RIKEN Center for Developmental Biology show that environmentally driven reprogramming of cells may resolve this controversy and provide a new source of stem cells that would assuage those ethical concerns.

Inspired by the ability of certain mature plant cells to revert to immature blastema cells in response to changes in the environment, Haruko Obokata and colleagues sought to determine whether simple environmental changes could similarly allow pluripotent cells to arise from differentiated animal cells. To test this hypothesis, the researchers isolated mature, differentiated cells from the spleens of mice carrying a gene allowing the researchers to visualize the expression Oct4, a protein factor that is critical for cellular reprogramming. After treating the differentiated cells with an acidic medium, the researchers observed substantial expression levels of the reprogramming factor.

What is perhaps most exciting about this research is that it not only avoids the controversial use of embryos, but also the genetic reprogramming involved in the creation of induced pluripotent stem cells from adult cells. After seven days of treatment with the acidic environment, cells expressing the Oct4 protein also expressed other pluripotency-related markers, a phenomenon that is typically observed in embryonic stem cells. These results led Obokata and colleagues to conclude that this method stimulating an external environment can successfully convert the differentiation state of somatic cells to pluripotency, a phenomenon the researchers call “stimulus-triggered acquisition of pluripotency” (STAP).

STAP is not quite a solution to the stem cell controversy—or at least, not yet. Obokata et al. point out several significant differences between STAP cells and typical embryonic stem cells in mice, including a relatively limited capacity for self-renewal. Still, these findings open the door to further research on stimulus-driven cellular reprogramming. The researchers note that the precise mechanism by which environmental stressors initiate cellular reprogramming and whether only specific types of stressors can have this effect remain uncertain. For now though, the discovery of STAP represents an important step towards the resolution of the stem cell ethics controversy.